A series of experiments are proposed to investigate the interactions between a membrane protein, cytochrome oxidase, and lipids. There are several techniques to be employed to study these interactions. A photoreactive lipid probe has been employed to determine which subunits of the protein are accessible to lipid. From the extent of labeling, the relative surface area each subunit presents to the protein can be estimated. A new fluorinated lipid probe has been constructed to establish the effect of protein on the motions of the lipid in small vesicles by fluorine magnetic resonance techniques. Deuterated lipid probes are used to establish these effects in large protein lipid particles by measurement of the residual quadrupolar coupling observed. Initial results show a temperature dependent interaction between lipid and protein such that the protein restricts the motion of a variable amount of lipid and protein phase transition temperature. Differential scanning calorimetry will also be employed to determine the energetics of these interactions. Initial studies suggest the interactions between protein and lipid are slow on the NMR time scale, both in vesicles and large particles. The importance of the energetics and dynamics of the interactions as they relate to the function of the protein will be investigated. Subsequent expansion of the ideas developed in this proposal to other membrane proteins is discussed.